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Repurposing in vitro approaches for screening anti-parasitic drugs against the brain-eating amoeba Naegleria fowleri

Martín-Escolano, Ruben, Yiangou, Lyto, Kazana, Eleanna, Robinson, Gary K., Michaelis, Martin, Tsaousis, Anastasios D. (2021) Repurposing in vitro approaches for screening anti-parasitic drugs against the brain-eating amoeba Naegleria fowleri. International Journal for Parasitology: Drugs and Drug Resistance, 17 . pp. 204-212. E-ISSN 2211-3207. (doi:10.1016/j.ijpddr.2021.10.003) (KAR id:91579)

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https://doi.org/10.1016/j.ijpddr.2021.10.003

Abstract

Naegleria fowleri is both a pathogenic and a free-living microbial eukaryote, responsible for the development of primary amoebic meningoencephalitis (PAM) in humans. PAM is a rapid, severe and fatal underestimated infectious disease, which has been reported in countries with warmer climates. The major drawbacks with PAM are the lack of effective therapies and delay in diagnosis. The current frontline treatment presents a low rate of recovery (5%) and severe adverse effects. For example, many drug candidates lack efficacy, since they do not effectively cross the blood-brain-barrier. Consequently, more effective drugs are urgently needed. Herein, we report a new in vitro method suitable for medium- and high-throughput drug discovery assays, using the closely related Naegleria gruberi as a model. We have subsequently used this method to screen a library of 1,175 Food and Drug Administration-approved drugs. As a result, we present three drugs (camptothecin, pyrimethamine, and terbinafine) that can be repurposed, and are anticipated to readily cross the blood-brain-barrier with activity against Naegleria species in therapeutically achievable concentrations. Successively, we integrated several in vitro assays that resulted in identifying fast-acting and high amoebicidal drugs. In conclusion, we present a new approach for the identification of anti-Naegleria drugs along with three potential drug candidates for further development for the treatment of PAM.

Item Type: Article
DOI/Identification number: 10.1016/j.ijpddr.2021.10.003
Uncontrolled keywords: Naegleria; brain-eating amoeba; PAM; drug screening; drug repurposing
Subjects: Q Science > QR Microbiology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Anastasios Tsaousis
Date Deposited: 15 Nov 2021 12:21 UTC
Last Modified: 08 Feb 2022 16:26 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/91579 (The current URI for this page, for reference purposes)
Robinson, Gary K.: https://orcid.org/0000-0003-2660-7778
Michaelis, Martin: https://orcid.org/0000-0002-5710-5888
Tsaousis, Anastasios D.: https://orcid.org/0000-0002-5424-1905
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